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Chronic Hepatitis b Patients Switch to tAf After Discontinuation of Nucleoside Analogue (CHANGE)

Primary Purpose

Chronic Hepatitis b, Hepatitis B Reactivation

Status
Recruiting
Phase
Phase 4
Locations
Taiwan
Study Type
Interventional
Intervention
Vemlidy
Sponsored by
National Taiwan University Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Hepatitis b focused on measuring HBV,clinical relapse,Vemlidy (TAF)

Eligibility Criteria

20 Years - 99 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria A. Switching therapy cohort

  1. Chronic hepatitis B patients receiving oral antiviral therapy (ETV, TDF) for at least 2 years, and fulfil the following NUCs discontinuation criteria (1)HBeAg-positive patients achieving HBeAg seroclearance, and received at least 1-year consolidation therapy (2) HBeAg-negative patients achieving undetectable HBV DNA for more than 1 year (on 3 occasions, 6 months apart)
  2. After NUC discontinuation, patients had a clinical relapse (HBV DNA > 2000 IU/mL, and ALT > 2x ULN)
  3. The retreatment regimen switches to TAF (within 3 months of clinical relapse)

B. Historical continuing therapy cohort

  1. Chronic hepatitis B patients receiving oral antiviral therapy (ETV, TDF) for at least 2 years, and fulfil the following NUCs discontinuation criteria (1) HBeAg-positive patients achieving HBeAg seroclearance, and received at least 1-year consolidation therapy (2) HBeAg-negative patients achieving undetectable HBV DNA for more than 1 year(on 3 occasions, 6 months apart)
  2. After NUC discontinuation, patients had a clinical relapse (HBV DNA > 2000 IU/mL, and ALT > 2x ULN)
  3. The patients continued the original regimen (ETV, TDF) for retreatment (within 3 months of clinical relapse)

Exclusion Criteria

  1. Patients who do not fulfill the discontinuation criteria
  2. Patients who have HCV, HDV or HIV co-infection
  3. Patients who discontinue lamivudine, adefovir, or telbivudine therapy
  4. Patients with liver cirrhosis by ultrasonography and clinical diagnosis

Sites / Locations

  • Buddhist Tzu Chi General Hospital, Da-Lin BranchRecruiting
  • Chia-Yi Christian HospitalRecruiting
  • National Taiwan University Hospital, Yun-Lin branchRecruiting
  • E-da hospitalRecruiting
  • National Taiwan University HospitalRecruiting
  • Buddhist Tzu-Chi General Hospital Taipei Branch
  • Taipei City Hospital, Renai BranchRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Switching therapy cohort

Historical continuing therapy cohort

Arm Description

single arm, open label Patients will receive Vemlidy (tenofovir alafenamide, TAF) 25mg, daily for 48 weeks

By retrospectively review medical records, The patients continued the original regimen (ETV, TDF) for retreatment (within 3 months of clinical relapse)

Outcomes

Primary Outcome Measures

Rate of virological remission (HBV DNA <20 IU/mL)
We will calculate the rate of virological remission (HBV DNA <20 IU/mL) after retreatment

Secondary Outcome Measures

Rate of ALT normalization (ALT < 40 U/L) after retreatment
We will calculate the rate of ALT normalization (ALT < 40 U/L) after retreatment
Rate of HBsAg change after retreatment compared with baseline
We will investigate the rate of HBsAg change after retreatment compared with the baseline HBsAg
Rate of HBcrAg change after retreatment compared with baseline
We will investigate the rate of hepatitis B core-related antigen (HBcrAg) change after retreatment compared with baseline HBcrAg
Rate of M2BPGi level change after retreatment compared with baseline
We will investigate the rate of Mac-2 binding protein glycosylation isomer (M2BPGi) level change after retreatment compared with baseline M2BPGi level

Full Information

First Posted
July 26, 2020
Last Updated
August 4, 2021
Sponsor
National Taiwan University Hospital
Collaborators
National Taiwan University Hospital, Yun-Lin Branch, Taipei City Hospital, Chiayi Christian Hospital, Dalin Tzu Chi General Hospital, E-DA Hospital, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation
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1. Study Identification

Unique Protocol Identification Number
NCT04496882
Brief Title
Chronic Hepatitis b Patients Switch to tAf After Discontinuation of Nucleoside Analogue
Acronym
CHANGE
Official Title
The Clinical Efficacy of Tenofovir Alafenamide-switching Therapy in Patients With Chronic Hepatitis B Experiencing Clinical Flare-up After Discontinuation of Nucleos[t]Ide Analogues Therapy
Study Type
Interventional

2. Study Status

Record Verification Date
August 2021
Overall Recruitment Status
Recruiting
Study Start Date
September 9, 2020 (Actual)
Primary Completion Date
December 31, 2022 (Anticipated)
Study Completion Date
December 31, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Taiwan University Hospital
Collaborators
National Taiwan University Hospital, Yun-Lin Branch, Taipei City Hospital, Chiayi Christian Hospital, Dalin Tzu Chi General Hospital, E-DA Hospital, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
We will conduct a phase 4, multicenter, open-label trial at 7 academic centers in Taiwan. Chronic hepatitis B patients receiving oral antiviral therapy (entecavir [ETV], tenofovir disoproxil fumarate [TDF]) for at least 2 years, and fulfil the following nucleos(t)ide analogs discontinuation criteria. After nucleos(t)ide analogs discontinuation, patients had a clinical relapse and retreatment regimen switches to TAF. The protocol will be approved by Institutional Review Board (IRB) or Research ethic committee (REC) of each site and will be conducted in accordance with the principles of Declaration of Helsinki and the International Conference on Harmonization for Good Clinical Practice. Each patient provides written informed consent before enrollment.
Detailed Description
Tenofovir alafenamide (TAF) is a new generation of oral antiviral drugs with similar antiviral activities to tenofovir disoproxil fumarate (TDF) and reduces the adverse effects of nephrotoxicity and bone mineral density reduction. This drug has already been reimbursed by National Health Insurance, and can be used for the treatment of patients with chronic hepatitis B. This is a single-arm prospective clinical trial to enroll patients who discontinued entecavir (ETV) and tenofovir disoproxil fumarate (TDF) and experienced a clinical hepatitis flare up. They can be retreated with TAF for 48 weeks without postponing a 3-month observation period for alanine aminotransferase (ALT) level. The virological control, ALT level recovery, and changes in liver fibrosis, hepatitis B surface antigen, hepatitis B core-associated antigen, and renal function will be observed during retreatment. In addition, a group of patients with the same characteristics who received retreatment with entecavir or TDF will be collected as a control group for comparison. We believe this study can help us understand the clinical benefits of switching to TAF for retreatment after hepatitis flare in patients to discontinue oral antiviral agents.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Hepatitis b, Hepatitis B Reactivation
Keywords
HBV,clinical relapse,Vemlidy (TAF)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
260 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Switching therapy cohort
Arm Type
Experimental
Arm Description
single arm, open label Patients will receive Vemlidy (tenofovir alafenamide, TAF) 25mg, daily for 48 weeks
Arm Title
Historical continuing therapy cohort
Arm Type
No Intervention
Arm Description
By retrospectively review medical records, The patients continued the original regimen (ETV, TDF) for retreatment (within 3 months of clinical relapse)
Intervention Type
Drug
Intervention Name(s)
Vemlidy
Other Intervention Name(s)
Tenofovir Alafenamide (TAF)
Intervention Description
25mg Tenofovir Alafenamide
Primary Outcome Measure Information:
Title
Rate of virological remission (HBV DNA <20 IU/mL)
Description
We will calculate the rate of virological remission (HBV DNA <20 IU/mL) after retreatment
Time Frame
48 weeks
Secondary Outcome Measure Information:
Title
Rate of ALT normalization (ALT < 40 U/L) after retreatment
Description
We will calculate the rate of ALT normalization (ALT < 40 U/L) after retreatment
Time Frame
48 weeks
Title
Rate of HBsAg change after retreatment compared with baseline
Description
We will investigate the rate of HBsAg change after retreatment compared with the baseline HBsAg
Time Frame
48 weeks
Title
Rate of HBcrAg change after retreatment compared with baseline
Description
We will investigate the rate of hepatitis B core-related antigen (HBcrAg) change after retreatment compared with baseline HBcrAg
Time Frame
48 weeks
Title
Rate of M2BPGi level change after retreatment compared with baseline
Description
We will investigate the rate of Mac-2 binding protein glycosylation isomer (M2BPGi) level change after retreatment compared with baseline M2BPGi level
Time Frame
48 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
99 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria A. Switching therapy cohort Chronic hepatitis B patients receiving oral antiviral therapy (ETV, TDF) for at least 2 years, and fulfil the following NUCs discontinuation criteria (1)HBeAg-positive patients achieving HBeAg seroclearance, and received at least 1-year consolidation therapy (2) HBeAg-negative patients achieving undetectable HBV DNA for more than 1 year (on 3 occasions, 6 months apart) After NUC discontinuation, patients had a clinical relapse (HBV DNA > 2000 IU/mL, and ALT > 2x ULN) The retreatment regimen switches to TAF (within 3 months of clinical relapse) B. Historical continuing therapy cohort Chronic hepatitis B patients receiving oral antiviral therapy (ETV, TDF) for at least 2 years, and fulfil the following NUCs discontinuation criteria (1) HBeAg-positive patients achieving HBeAg seroclearance, and received at least 1-year consolidation therapy (2) HBeAg-negative patients achieving undetectable HBV DNA for more than 1 year(on 3 occasions, 6 months apart) After NUC discontinuation, patients had a clinical relapse (HBV DNA > 2000 IU/mL, and ALT > 2x ULN) The patients continued the original regimen (ETV, TDF) for retreatment (within 3 months of clinical relapse) Exclusion Criteria Patients who do not fulfill the discontinuation criteria Patients who have HCV, HDV or HIV co-infection Patients who discontinue lamivudine, adefovir, or telbivudine therapy Patients with liver cirrhosis by ultrasonography and clinical diagnosis
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Tung-Hung Su, MD, PhD
Phone
886972651694
Email
tunghungsu@gmail.com
First Name & Middle Initial & Last Name or Official Title & Degree
Pei-Ying Yang, MS
Phone
886965277228
Email
pying0208@gmail.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Tung-Hung Su, MD, PhD
Organizational Affiliation
National Taiwan University Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Buddhist Tzu Chi General Hospital, Da-Lin Branch
City
Chiayi City
Country
Taiwan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kuo-Chih Tseng, MD
Phone
88652648000
Ext
3240
Email
tsengkuochih@gmail.com
Facility Name
Chia-Yi Christian Hospital
City
Chiayi City
Country
Taiwan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Chi-Yi Chen, MD
Phone
88652765041
Ext
5264
Email
5137ccy@gmail.com
Facility Name
National Taiwan University Hospital, Yun-Lin branch
City
Douliu
Country
Taiwan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yu-Jen Fang, MD
Phone
886972655715
Email
toby851072@gmail.com
Facility Name
E-da hospital
City
Kaohsiung
Country
Taiwan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yao-Chun Hsu, MD, PhD
Phone
886975209520
Email
holdenhsu@gmail.com
Facility Name
National Taiwan University Hospital
City
Taipei
ZIP/Postal Code
100
Country
Taiwan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Tung-Hung Su, MD, PhD
Phone
886972651694
Email
tunghungsu@gmail.com
Facility Name
Buddhist Tzu-Chi General Hospital Taipei Branch
City
Taipei
Country
Taiwan
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Chia-Chi Wang, MD
Phone
886266289779
Ext
2317
Email
uld888@yahoo.com.tw
Facility Name
Taipei City Hospital, Renai Branch
City
Taipei
Country
Taiwan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Chih-Lin Lin, MD
Phone
886227099558
Email
lcl@tpech.gov.tw

12. IPD Sharing Statement

Plan to Share IPD
No

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Chronic Hepatitis b Patients Switch to tAf After Discontinuation of Nucleoside Analogue

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